RESEARCH PROPOSAL: Notch is a transmembrane protein with multiple EGF- like repeats in the extracellular domain and ankryn repeats in the cytoplasmic domain. During embryogenesis, Notch function is required to suppress neuronal differentiation and in the absence of Notch neurons are overproduced at the expense of epidermal cells. Vertebrate Notch homologs are known and are also implicated in neural development and are associated with certain cancer syndromes. Notch may also function in regulating c ell adhesion as Notch interacts directly with the disheveled protein and thereby antagonizes wingless and cadherin signaling. Dr. Piepenhagen proposes to study the role of Notch subcellular localization in its function. First he plans to determine whether Notch is associated with septate or adherens junctions in Drosophila wing discs. Then he proposes to examine which domain of the Notch protein is essential for this function by looking at the localization of deleted forms of Notch and by looking to see if any domain of Notch can confer Notch-like localization to a heterologous membrane protein. The rationale is solid, the experiments are technically straightforward and the studies should provide some fundamentally new insight into Notch structure and function.